The present inventors have made an exploratory research on new camptothecin (hereinafter referred to CPT) derivatives with excellent anti-tumor activities and already provided many CPT derivatives, and it has been found out that in particular a group of derivatives prepared by a totally synthetic method have an excellent activity, which have a lower alkyl group in 7-position on the B-ring and various hetero substituents and an alkyl group in 9-, 10- and 11-position on the A-ring (see JP, A, H1-186892, U.S. Pat. No. 5,061,800). The present inventors have also made a development research for a method to make them water-soluble by various means in order to solve an administration problem, and found that regarding especially 7-ethyl CPT, the derivatives, in which the part of E-lactone ring is opened by use of the diamine and the hydroxymethyl group is protected by the appropriate acyl group, are excellent in the water solubility without decrease of an anti-tumor activity, contrasting to the E-ring opened water-soluble CPT derivatives known previously (see JP, A, H1-131179, U.S. Pat. No. 4,914,205).
Further, a new group of derivatives which were water-soluble and excellent in an anti-tumor activity were prepared and provided by derivatizing a group of derivatives having a lower alkyl group in 7-position on the B-ring and various hetero substituents and an alkyl group in 9-, 10- and 11-position on the A-ring into derivatives in which the E-lactone ring part is opened by the diamine and further the hydroxymethyl group is protected by an appropriate acyl group (see JP, A, H8-73461, AU, Pat. No. 688547). However, though these derivatives solve the water solubility problem, they are unstable in a basic water solution and not necessarily suitable for making a preparation such as an oral administration agent.
While realizing the water solubility favorable for administration, the creation of a new CPT derivative is needed which is excellent in an anti-tumor activity and in the stability in a basic water solution.